Chitosan is a natural polymer which is obtained by N-deacetylating a polysaccharide chitin in a conc. alkaline solution, said chitin being present in abundance in the exoskeleton of crustaceans or insects, and chitosan per se has been used as a colonic delivery substance because it disintegrates specifically by Escherichia coli. Several pharmaceutical compositions containing chitosan, which can release the medicament therefrom specifically in the large intestine, have been known hitherto.
For instance, JP-A-4-69333 discloses a colonic delivery solid preparation, which is obtained by successively coating a solid medicament with a chitosan layer and an enteric coating layer containing as a main material hydroxypropyl methylcellulose acetate succinate or hydroxypropyl methylcellulose hexahydrophthalate.
JP-A-7-2701 discloses a pharmaceutical composition comprising a micronized cellulose and a water-soluble chitosan having a deacetylation degree of 40-60 mole % in a ratio of 20 to 200% by weight to the amount of the micronized cellulose, which can pass through the small intestine and disintegrate in the large intestine, and a process for producing the same.
Since chitosan is usually soluble only in an acidic aqueous solution but hardly soluble in an organic solvent, it is necessary to dissolve chitosan in an acidic aqueous solution in order to use it for coating a naked solid preparation in the process of preparing a colonic delivery solid preparation. However, it is very difficult to completely remove the acid contained in the acidic aqueous solution of chitosan after the coating step, and it cannot be helped for the acid to remain in the chitosan coating film, which causes some problems such as reduction of water resistant of the chitosan coating film and the harmful effects of the acid on the medicament per se. In order to overcome these defects, the above-mentioned JP-A-4-69333 suggests forming in advance an enteric coating film inside of the chitosan layer, but this method needs an extra coating step and hence it is not desirable.
In addition, in the above-mentioned JP-7-2701, various harmful results due to the acid used in the dissolution of chitosan are avoided by using a water-soluble chitosan having a deacetylation degree of 40-60%. However, when such a water-soluble chitosan is used, it is difficult to control the release of the medicament in the large intestine, while the solid preparation of the present invention can make it possible as mentioned below.